Axotomized, mature neurons that do not regenerate enter an apparently involutional state that is refractory to further axonal growth. Little information is available about the expressionof gene products in neurons that have assumed such a state, and about what extent the composition of gene products expressed while in an involutional state may differ from that in a normal, intact state and in a state in which axonal growth is actively supported. AFter a conditioning optic nerve crush in goldfish, retinal explants from such animals yield a rich outgrowth of retinal ganglion cell axons in vitro, which remain free of glial cells when explants are cultured in the presence of 5-fluorodeoxyuridine. Survival of the axonal outgrowth (i.e., axonal field) in vitro, however, is limited. Typically, the explant undergoes four sequential phases that can be designated as follows: (1) active axonal growth; (2) cessation of axonal growth and senescence of the axonal field; (3) axonal degeneration; and (4) ganglion cell involution. This proposal is concerned with characterizing quantitative and qualitative compositional changes in protein synthesis of axotomized ganglion cells of goldfish retinal explants in vitro during each of the four principal phases. Analyses of composition of proteins and RNA transported into axonal fields during active axonal growth and during senescence of axonal fields will also be undertaken. Attempts will be made to determine whether axonal transport ceases in advance of degeneration of axonal fields, and determine, thereby, whether cessation of transport may contribute to degeneration. Finally, experiments will be undertaken to re-induce axonal growth after ganglion cells have entered an involuted state. If the latter experiments are successful, then the expression of gene products will be studied during the period of induction. To ensure purity of samples, cell-free, isolated axonal fields and microdissected retinal ganglion cells will be analyzed on a microscale. The proposed research will deal with an important basic question as to whether expression of gene products governs the growth-related state of the neuron. The outcome should help to decide whether control of neuronal growth is genetic or epigenetic.